Houghton, John - Georgia State University

个人简介

Ph.D. Biochemistry Texas A&M University 1986 Molecular Genetics and Biochemistry Applied and Environmental Microbiology Yeast Genetics/ Cellular Responses

研究领域

Research in the laboratory is centred around mechanisms that underpin cellular response(s) to changes in the environment. The research has two quite distinct components: the one uses Saccharomyces cerevisiae as a model eukaryotic system to evaluate the cellular response to heavy metal exposure, such as Copper, Chromium (VI) and Cadmium. The other investigates the role of transcriptional regulatory circuits within Pseudomonas putida, which coordinate both the cell’s metabolic and chemotactic response(s) to the presence of aromatic hydrocarbons. Oxidative Targeting of Enzymes in S. cerevisiae: While both cellular response mechanisms differ dramatically in their mechanisms of action, they each share a significant metabolic component. The first level response of S. cerevisae to exposure to sub-lethal concentrations of heavy metals involves targeted oxidation of enzymes predominantly within the glycolytic pathway ( Figure 1). Figure 1: The Glycolytic and Pentose Phosphate pathways in S. cerevisiae, showing the key enzymes and reactions (in red) that appear to be specifically targeted for oxidation in response to the presence of heavy metals, such as Cu, Cd and Cr. Such targeting is believed to result in an immediate -but transient- decrease in glycolytic enzyme activity, possibly resulting in a catabolic shift of carbon flow away from glycolysis and into the pentose-phosphate pathway -to generate NADPH2 that can be utilized to combat the oxidative insult. Work in the lab is presently focused upon this and other cellular responses to heavy metals that affect protein expression (Figure 2); namely transcriptional levels of key enyzmes and regulatory proteins (Figure 2: underlay). Figure 2: A 2-dimensional display of cellular protein expression from S. cerevisiae cells, following exposure to sub-lethal levels of Chromium. cells, following exposure to sub-lethal levels of Chromium. Underlay: A graphical representation of RTPCR analyses, showing the temporal expression of key glycolytic enzymes, pentose phosphate pathway enzymes and transcriptional / translational regulatory genes in response to the presence of heavy metals. Additional avenues of research, which are actively being pursued in the laboratory are: (1) Regulation of ornithine utilization within P. aeruginosa and (2) Regulation of Bioremediatory processes in pseudomonads

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Phospholipids induce conformational changes of SecA to form membrane-specific domains: AFM structures and implication on protein-conducting channels. You Z, Liao M, Zhang H, Yang H, Pan X, Houghton JE, Sui SF, Tai PC. PLoS One. 2013 Aug 16;8(8):e72560. doi: 10.1371/journal.pone.0072560. eCollection 2013. Cadmium induces a heterogeneous and caspase-dependent apoptotic response in Saccharomyces cerevisiae. Nargund AM, Avery SV, Houghton JE. Apoptosis. 2008 Jun;13(6):811-21. doi: 10.1007/s10495-008-0215-8. Oxidative protein damage causes chromium toxicity in yeast. Sumner ER, Shanmuganathan A, Sideri TC, Willetts SA, Houghton JE, Avery SV. Microbiology. 2005 Jun;151(Pt 6):1939-48. Copper-induced oxidative stress in Saccharomyces cerevisiae targets enzymes of the glycolytic pathway. Shanmuganathan A, Avery SV, Willetts SA, Houghton JE. FEBS Lett. 2004 Jan 2;556(1-3):253-9. Cell cycle- and age-dependent activation of Sod1p drives the formation of stress resistant cell subpopulations within clonal yeast cultures. Sumner ER, Avery AM, Houghton JE, Robins RA, Avery SV. Mol Microbiol. 2003 Nov;50(3):857-70. The involvement of nurses in reporting suspected adverse drug reactions: experience with the meningococcal vaccination scheme. Ranganathan SS, Houghton JE, Davies DP, Routledge PA. Br J Clin Pharmacol. 2003 Dec;56(6):658-63. PcaR-mediated activation and repression of pca genes from Pseudomonas putida are propagated by its binding to both the -35 and the -10 promoter elements. Guo Z, Houghton JE. Mol Microbiol. 1999 Apr;32(2):253-63. Regulation of ornithine utilization in Pseudomonas aeruginosa (PAO1) is mediated by a transcriptional regulator, OruR. Hebert MD, Houghton JE. J Bacteriol. 1997 Dec;179(24):7834-42.